The basic probelms in the interaction of mineral and collagen are not clearly understood at this time. The objective of these studies is to continue a search into the mechanisms of how the body handles mineral and mineralized collagen at a physiological and biochemical level during various ages. We have obtained evidence in vivo which will aid in elucidating the molecular and supermolecular turnover of mineral and collagen under normal and pathological conditions in young and adult rats and dogs. The experimental design is to study the fate of mineral and mineralized collagen macromolecules qualitatively and quantitatively in chronically labeled animals over short and long intervals of time after labeling and when the animal has reached a steady state, isotopically and biologically. Since the phenomena of collagen destruction and collagen reutilization, and calcium loss and calcium conservation are both known to exist, these studies should add in estimating the relative proportion between destructive and non-destructive bone turnover. This work will be done for: (1) embryonic or neonatal bone in vitro; (2) different biological conditions in vivo: external growth remodelling, internal remodelling, fracture remodelling, and disuse remodelling; and (3) during aging. The concept of non-isotopic turnover of macromolecules would provide a new biological basis for studying growth and fracture remodelling, and aging; and for elucidating the biologic controls between destructive and non-destructive turnover of mineralized collagen and mineral.